This invention is in the area of polymer chemistry, and in particular is a method for the sulfonation of cyclic trimer and polymeric phosphazenes, and the products produced thereby.
The design and synthesis of hydrophilic or water-soluble polymers is of considerable technological interest for a wide range of applications, including for metal chelation and the preparation of anti-static materials. Hydrophilicity is also an important factor in the surface behavior of biomedical materials. Sulfonic acid groups are one of the more important substituent groups used to impart hydrophilic character to a polymer. Polymers that bear sulfonic acid groups are currently used in ion-exchange resins, nonthrombogenic biomaterials, reverse osmosis membranes anti-static materials, and bacteriostats.
Polyphosphazenes are a broad class of macromolecules based on the repeating unit (NPR.sub.2)n. One of the primary methods for the synthesis of these polymers is illustrated in Scheme I. Poly(dichlorophosphazene) (2) reacts with a wide variety of nucleophiles to yield high molecular weight polymers with properties that vary widely based on the structure of the substituent. The stability of the phosphorus-nitrogen backbone makes this class of macromolecules particularly suitable for side group and surface modification.
Examples of poly(organophosphazenes) and methods for their synthesis include those described in U.S. Pat. No. 4,440,921, which discloses that biologically active molecules containing a carboxylic acid residue can be covalently attached to a polyphosphazene via condensation with a pendant amino group on the polyphosphazene (see also Allcock, H. R.; Hymer, W. C.; Austin, P. E. Macromolecules 1983, 16, 1401); U.S. Pat. No. 4,880,622 which discloses novel poly(organophosphazene)s that are useful for the controlled delivery of pharmaceuticals, pesticides, herbicides, plant growth regulators, and fertilizers; U.S. Pat. No. 5,053,451 which discloses that poly(carboxylatophenoxy)phosphazene can be ionically cross-linked to form a hydrogel; and U.S. Pat. No. 5,149,543 which discloses a composition that includes a biological material such as a liposome, virus, procaryotic cell, or eucaryotic cell encapsulated in an ionically cross-linked poly(organophosphazene) or other polyelectrolyte. ##STR1##
The surface sulfonation of aryloxy- and arylaminophosphazenes has been accomplished with concentrated sulfuric acid (Scheme II, reaction A; Allcock, R. R. et al., 1991, Chem Mater. Vol. 3, p 1120). Aryloxypolyphosphazenes can also be sulfonated with sulfur trioxide (Monotoneri, E. et al., 1989, Macromol. Sci. Chem. Vol. A26, No. 4, p 645, Monotoneri. E. et al., 1989, Macromol. Chem. Vol. 190, p 191). However, aryloxy and arylamino polyphosphazenes are rigid polymer systems with high glass transition temperatures. The rigid character of these polymers decreases their use for many applications in which elastic behavior is desired.
Polymers that contain etheric substituent groups are useful as biomaterials, as polyelectrolytes and in battery applications, among others. Sulfonation of ether containing polymers can provide materials with enhanced biocompatibility and conductivity. Sulfonated etheric polyphosphazenes can be grafted onto the surface of other polymers via ultra-violet (UV), gamma, or electron beam irradiation to provide composite materials with a range of properties for a number of applications.
Polyphosphazenes with etheric substituent groups cannot be sulfonated with sulfuric acid or sulfur trioxide because etheric polyphosphazenes decompose in acidic conditions. Polyphosphazenes with etheric side groups and sulfonic acid groups have been synthesized by Shriver and coworkers via the reaction of sodium ethoxy sulfonate with poly(dichlorophosphazene), followed by ##STR2## treatment with a second etheric nucleophile (Scheme II, reaction B; Ganapethiappan, S. et al., 1988, Macromolecules, Vol. 21, p 2299). This method has several limitations. First, sodium ethoxy sulfonate has only a limited solubility in the etheric solvents used for the reaction. Second, the use of a difunctional reagent results in crosslinking of the polymer chains. Although the crosslinks can be broken by the addition of a second nucleophile, this introduces an unwanted complication to the process. This reaction is also limited by the premature precipitation of the polymers from solution. The most obvious disadvantage of this system is the inability to carry out surface reactions. The sulfonation must be performed on the bulk polymer in solution. Surface sulfonation of polymers is desirable for the preparation of certain biomaterials, especially those used as prosthetic devices inside the body. Surface sulfonation increases blood compatibility, while enabling the bulk of the material to remain unsulfonated and therefore retain its specific properties, such as elasticity.
An improved synthetic approach to the sulfonation of polyphosphazenes would be useful in the development of new biomedical materials, membranes, reversibly cross-linkable polymers, surfactants, controlled drug release devices, such as microparticles and nanoparticles that encapsulate a substance to be delivered, new ion exchange resins, antistatic materials, and coatings for electronics and polyelectrolytes.
Therefore, it is an object of the present invention to provide a new method for the sulfonation of polymeric and cyclic trimer phosphazenes.
It is another object of the present invention to provide a method for the sulfonation of phosphazenes that can be carried out as a bulk or surface reaction.
It is another object of this invention to provide a new class of sulfonated polyphosphazenes for use a biomaterials, antistatic agents, polyelectrolytes, and for other applications.